Preparation, preliminary pharmacokinetics and brain tissue distribution of Tanshinone IIA and Tetramethylpyrazine composite nanoemulsions WangBeilei HongLufeng LiuYuanxu BedingfieldSean K. ZhangCaiyun PengCan QianJiajia ZhaLiqiong 2019 <p><b>Objective:</b> Tanshinone IIA (TSN) and Tetramethylpyrazine (TMP) were combined in a composite, oil-in-water nanoemulsions (TSN/TMP O/W NEs) was prepared to prolong <i>in vitro</i> and <i> vivo</i> circulation time, and enhance the bioavailability of TSN.</p> <p><b>Material and methods:</b> Physicochemical characterization of TSN/TMP O/W NEs was characterized systematically. The <i>in vitro</i> dissolution and <i>in vivo</i> pharmacokinetic experiments of TSN/TMP O/W NEs were also evaluated.</p> <p><b>Result:</b> A formulation was optimized, yielding a 32.5 nm average particle size, an encapsulation efficiency of over 95 %, and were spherical in shape as shown by TEM. TSN/TMP O/W NEs were shown to extend the release and availability <i>in vitro</i> compared to raw compounds. In pharmacokinetic study, the AUC<sub>0→∞</sub> and <i>t</i><sub>1/2</sub> of the TSN/TMP O/W NEs were 481.50 mg/L*min and 346.39 min higher than TSN solution, respectively. Brain tissue concentration of TSN was enhanced with TSN/TMP O/W NEs over raw TSN and even TSN O/W NEs.</p> <p><b>Conclusions:</b> Therefore, nanoemulsions are an effective carrier to increase encapsulation efficiency of drugs, improve bioavailability and brain penetration for TSN – which is further enhanced by pairing with the co-delivery of TMP, providing a promising drug delivery.</p>